Combined effects of captopril and the diuretic trichloromethiazide on blood pressure in patients with essential hypertension

Various doses (5, 12.5 and 25 mg) of angiotensin I converting enzyme inhibor (captopril) were administered orally alone and following pretreatment with 2 mg of trichloromethiazide (TH) in patients with essential hypertension. The time courses of mean blood pressure (MBP), plasma renin activity (PRA), and plasma angiotension I converting enzyme activity (ACE) were determined for 3 hr after the administration. The blood concentration of captopril (BCC) following the drug admini-stration was also determined. The basal MBP before captopril administration was unchanged by pretreatment with TH for 4 days. Each dose of captopril administered alone induced a decrease in MBP in a dose-dependent manner and the administration combined with TH enhhaced the hypo-tensive effect of the drug. The mean values of PRA following 5 and 12.5 mg of the drug without TH were similarly increased, although statistically significant changes were not observed in either case. The response of PRA following 25 mg of the drug alone was greater than that following 5 or 12.5 mg of the drug alone, although there was no statistically significant increase. Pretreatment with TH enhanced the basal levels of PRA and induced large responses in PRA to 12.5 and 25 mg of captopril. The ACE was lowered by each dose of captopril in a dose-dependent manner and the degree of the decreases was not influenced by pretreatment with TH. Pharmacokinetic analysis was undertaken for the area under the blood concentration curve (AUC), maximum concentration (C max), maximum concentration time (T max) and biological half-life (T 1/2). These generally varied in a dose-dependent manner. However, the AUC and C max at 12.5 mg of captopril with TH were significantly higher than those without TH. The results of the present study emphasize the effective hypotensive action of combined therapy of captopril, even at a small dose, with diuretics. The questionable relationship between the clinical action and pharmacokinetics of captopril remains.